Senna is a common term that typically refers to dried leaflets of the plant Cassia senna L. (synonym: C. angustifolia Vahl, C. angustifolia Delile, and C. acutifolia Defile). Upon ingestion, very little of the senna active substances are systemically absorbed by the body. Senna contains anthraquinones, including diathrone glycosides, sennosides A and B (rhein diathrones), sennosides C and D (rhein aloe emodin heterodianthrones), and other minor sennoside compounds, which all seem to contribute to a laxative effect in humans. Sermosides A and B are of particular utility in creating a laxative effect and have been used in the production of medicinal cathartic preparations. Senna contains hydroxyanthracene glycosides that are not fully absorbed in the upper gastrointestinal tract are converted into active aglycones by mircoflora in the large intestine and additional bacterial enzymes in the colon, which stimulates colonic motility and affects fluid and electrolyte balance in the colon.
Similarly, anthraglycosides found in alder buckthorn (Frangula alnus, synonym: Rhamnus frangula) and cascara products (Frangula pershiana, synonym: Rhamnus persiana) have cathartic properties; such examples to name few are Cascara sagrada, buckthorn bark, bitter bark, chittem bark, yellow bark, dogwood bark, Rhamni pershianae Cortex, and sagrada bark. Cascara sagrada contains cascarosides A and B (anthraglycosides), which are responsible for increased peristalsis in the large intestine. Cathartic preparations of Cascara sagrada extracts are standardized to contain 25% to 30% hydroxyanthracene derivatives per dose. Casanthranol A and B (anthranol glycosides) derived from Cascara sagrada are used in cathartic preparations. Casanthranol A and B upon oxidative hydrolysis yield more active anthraquinone aglycones and glycosides, i.e., cascarosides A (emodin) and B (aglycone) forms of anthraglycosides.
The use of senna and other plant-derived cathartics dates back to about the 9th century A.D. when physicians medicinally employed senna, for example, as a cathartic; the leaves were brewed into a tea and the tea was administered to patients for its strong laxative effect. Today, senna and other plant species are still typically administered as aqueous infusions. For example, an herbal tea of Chinese mallow senna leaf (Cassia angustifolia), is prepared by steeping the leaves in hot water. Several disadvantages of such teas are (1) its unpleasant taste and appearance, and (2) the inconvenient and extended time (up to 20 minutes) needed for the preparation of the tea before it is steeped sufficiently, of efficacious strength, cooled sufficiently, and then ready to drink.
Problems with laxatives include their overall effectiveness as well as the unpredictable amount of time from ingestion to laxative action for the user. Delivering a useful active stimulant laxative product to various sections of the gastrointestinal tract in high enough concentration to have clinical effect is desirable, yet overdosing and localized high concentrations of active laxative product can yield adverse cramping effects in the upper gastrointestinal tract (duodenum and jejunum), when strong peristalsis is desired globally in the lower gastrointestinal tract, i.e. the ileum and colon. Therefore, poorly prepared delivery of solid oral dosage systems of herbal laxatives (e.g., encapsulated senna leaf powder) and OTC laxative drugs (e.g., poorly dissolving tablets) have their shortcomings in efficacy to affect motility of the ileum and colon in part because of pharmacodynamic delivery.
For instance, various encapsulated senna leaf powders count on the body's gastrointestinal tract to “steep the tea” into solution in vivo where the stomach is a highly acidic pH environment. This leads to slow solubility of active laxative compounds and may lead to localized high concentrations where the Senna leaf powder may settle in contact with the lumen of the gastrointestinal tract versus global lumen surface contact. Drinking a senna tea would be more efficacious than ingesting an encapsulates senna leaf powder but on the other hand is much less convenient than a capsule, and the taste is unpleasant.
The formulation of plant-derived laxatives in effervescent compositions has not been described previously, though effervescent compositions and processes are known. For example U.S. Pat. No. 7,247,324 B1 describes methods for delivering guava extract using effervescent formulations; US Patent application 2010/0215758 A1 describes effervescent formulations for the delivery of polyunsaturated fatty acids; U.S. Pat. No. 6,764,696 B2 pertains to the effervescent formulations of drugs, to increase the bioavailability of drugs in different parts of the gastrointestinal tract including esophagus, duodenum and colon; US 2006/0039973 A1 provides an effervescent composition for the delivery of dietary fiber; U.S. Pat. No. 5,498,425 describes a phosphosoda buffered saline laxative containing pineapple flavoring; U.S. Pat. No. 5,514,663 pertains to laxative enteric coated compositions of sennosides with the express purpose of releasing the sennosides substantially near the junction between the small intestine and the colon or within the colon; U.S. Pat. No. 6,083,531 describes effervescent formulations that disintegrate rapidly, within 15 seconds, in the mouth to deliver pain medications and other drugs.
Another notable problem with conventional delivery of plant-derived laxatives and other medically valuable plant derivatives is the solubility and the presence, concentration, and location of the biologically active plant derivatives. For example, hydroxyanthracene glycosides that are not fully absorbed in the upper gastrointestinal tract are converted into active aglycones by mircoflora in the large intestine. Another problem is the overuse of antibiotics, wherein the gastrointestinal tract loses symbiotic commensal microorganisms that produce catalytic enzymes. Such enzymes help activate plant-derived cathartic compound and derivatives into biologically active laxative derivatives. Administering probiotic and enzyme products can facilitate the effectiveness of plant-derived cathartics and their derivative compounds.
The following references are believed to describe the state of the art concerning (a) Cassia senna, (b) Cascara (Rhamnus persiana), including Cascara sagrada and buckthorn bark, (c) Lactobacillus bacteria (genus) including L. acidophilus, and (d) Bifidobacteria (28 species) including B. bifidum (bifidus), B. lactis, and B. spp: Brinker F., Herb Contraindications and Drug Interactions, Sandy O R: Eclectic Medical Publication, 1998, 70; Newall C A, Anderson L A, and Phillipson J D, Herbal Medicines: A Guide for Health Care Professionals, London, England: The Pharmaceutical Press, 1996, 243-4; Bradley P R, ed, British Herbal Compendium, Vol. 1, Bournemouth, England: British Herbal Medicine Association, 1992, 52-4; Petticrew M, Watt I, and Sheldon T, “Systematic Review of the Effectiveness of Laxatives in the Elderly,” Health Technol Assess, 1997, 1(13): i-iv, 1-52; Balsari A, Ceccarelli A, Dubini F, et al, Microbiologica, 1982, 5(3): 185-94; Elmer G W, Am J Health Syst Pharm, 2001, 58(12):1101-9; Favier C, Neut C, Mizon C, et al, Dig Dis Sci, 1997, 42(4):817-22; Gibson G R and Wang X, J Appl Bacteriol, 1994, 77(4):412-20; Saaverdra J M, Bauman N A, Oung I, et al, “Lancet, 1994, 344(8929):1046-9; and Van der Wiel-Korstanje J A and Winkler K C, J Med Microiol, 1975, 8(4):491-501.
In view of the discussion set forth above, it is clear that a need exists for an improved dosage form of plant-derived cathartics.